Sandhu MS et al. (2008) LDL-cholesterol concentrations: a genome-wide association study. Lancet 371: 483–491

Studies have shown that elevated LDL cholesterol levels increase the risk of cardiovascular disease. Therapeutic strategies that target and control the biological mechanisms and regulation of LDL cholesterol metabolism might, therefore, be beneficial. Sandhu and colleagues performed a genome-wide association study to identify single-nucleotide polymorphisms (SNPs) that are linked to high LDL cholesterol levels.

The analysis included data for 293,461 autosomal SNPs in up to 11,685 patients from five studies; replication studies were also performed in two additional, independent populations to confirm the findings.

Overall, 21 SNPs were significantly associated with circulating LDL cholesterol levels. Most of these SNPs were located near to genetic loci with known involvement in LDL cholesterol metabolism (e.g. APOB and APOE genes); notably, however, three of the SNPs (rs599839, rs4970834 and rs646776) were located in close proximity to each other in the chromosome region 1p13.3. Linkage disequilibrium plots indicated that rs599839, the SNP with the strongest LDL cholesterol association, is located close to the CELSR2 and PSRC1 genes on chromosome 1. Compared with the major alleles, the minor alleles of all three SNPs (frequency 19–21%) were associated with significantly lower levels of LDL cholesterol.

The authors suggest that chromosome region 1p13.3 contains a locus that is related to LDL cholesterol metabolism, and that their findings might be useful for advancing our understanding of the regulation of LDL cholesterol concentrations.